Transcriptional cooperation between NF-kappaB p50 and CCAAT/enhancer binding protein beta regulates Nur77 transcription in Leydig cells.


  • Date de publication : 2009-01-29

Référence

El-Asmar B, Giner XC, Tremblay JJ. Transcriptional cooperation between NF-kappaB p50 and CCAAT/enhancer binding protein beta regulates Nur77 transcription in Leydig cells. J. Mol. Endocrinol. 2009;42:131-8. doi: 10.1677/JME-08-0016. PubMed PMID: 18996961.

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Mot(s) Clé(s)

animals base pairing base sequence ccaat-enhancer-binding protein-beta conserved sequence dna-binding proteins electrophoretic mobility shift assay leydig cells male mice molecular sequence data nf-kappa b p50 subunit nuclear receptor subfamily 4, group a, member 1 protein binding rats receptors, steroid response elements transcription, genetic

Résumé

Expression of steroidogenic enzyme-encoding genes in testicular Leydig cells is complex and involves several transcription factors including the orphan nuclear receptor NUR77 (NR4A1) and the bZIP factor CCAAT/enhancer binding protein beta (EBPbeta). How these transcription factors are integrated into a functional network, however, remains to be fully understood. Here, we report that the transcription factor C/EBPbeta can activate the Nur77 promoter as revealed by transient transfections in MA-10 Leydig cells. Through 5' progressive deletions and site-directed mutagenesis, the C/EBPbeta-mediated activation of the Nur77 promoter was found to be dependent on a novel species-conserved C/EBP element located at -110 bp. We also demonstrate using electromobility shift assay that C/EBPbeta specifically binds to this element. Furthermore, we report a functional cooperation between C/EBPbeta and the p50 subunit of NF-kappaB that involves a previously uncharacterized kappaB element located at -18 bp. Promoter analysis revealed that either the C/EBP or the kappaB element was sufficient to sustain the C/EBPbeta-p50 cooperation thus suggesting that both factors physically interact. Altogether, our results provide new data regarding Nur77 transcription in testicular Leydig cells in addition to providing new insights into the interplay between transcription factors involved in Leydig cell gene expression and function.